Paricalcitol + Chemotherapy for Pancreatic Cancer

No longer recruiting at 1 trial location

Overseen By Kimberly Perez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Thiazide diuretics, CYP450 3A inducers

Disqualifiers: Brain metastases, Hypercalcemia, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of adding paricalcitol (a form of vitamin D) to standard chemotherapy for individuals with untreated, metastatic pancreatic cancer. The study compares the outcomes of patients receiving regular chemotherapy alone versus chemotherapy combined with either an IV or oral form of paricalcitol. Individuals diagnosed with metastatic pancreatic cancer who have not yet received treatment may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires you to stop taking vitamin D and calcium supplements, as well as thiazide diuretics (a type of medication for high blood pressure) before starting the treatment. Additionally, you cannot take medications that affect the CYP450 3A enzyme, so you should check with your doctor about any other medications you are taking.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that paricalcitol, when combined with gemcitabine, is safe for patients with advanced cancer at doses up to 7 mcg/kg weekly through an IV, indicating that the treatment is generally well-tolerated. However, paricalcitol is not yet approved by the FDA for treating pancreatic cancer.

Both IV and oral forms of paricalcitol are being tested with gemcitabine and nab-paclitaxel to enhance the effectiveness of standard chemotherapy. While research continues, current studies offer some reassurance about the safety of paricalcitol with these drugs.

Prospective trial participants should consult a healthcare professional about any concerns. This discussion can help clarify how the information may relate to their situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they introduce paricalcitol, a form of vitamin D, into the mix. This is different from standard treatments like gemcitabine and nab-paclitaxel alone. Paricalcitol may help by modulating the immune system and potentially making cancer cells more sensitive to chemotherapy. Additionally, the trial explores two ways of administering paricalcitol: intravenously and orally, which could offer flexibility in treatment plans. This novel approach could lead to more effective strategies in combating pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that the combination of gemcitabine and nab-paclitaxel is already approved and effective for treating advanced pancreatic cancer. Studies have found that this combination can improve patient outcomes. This trial tests whether adding paricalcitol, administered either through an IV or as a pill, can enhance these results. Participants in one arm of the trial will receive gemcitabine and nab-paclitaxel with a placebo, while others will receive the same chemotherapy combination with paricalcitol, either intravenously or orally. Although paricalcitol is not yet approved for pancreatic cancer, early research is exploring its potential benefits when added to the usual chemotherapy treatment. These trials aim to determine if paricalcitol can enhance the treatment's effectiveness against pancreatic cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Kimberly Perez, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with previously untreated, metastatic pancreatic cancer. They should have measurable disease, be in good physical condition (ECOG ≤1), and have normal organ/marrow function. Participants must not have had chemotherapy for advanced pancreatic cancer or certain other treatments recently and agree to use contraception.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Agreement to use adequate contraception for the duration of study participation

My cancer is a type of pancreatic cancer that has spread to distant parts of my body.

Exclusion Criteria

I have high calcium levels in my blood.

I have had painful kidney or bladder stones in the last year.

I have severe nerve pain or numbness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate the safety of adding paricalcitol to gemcitabine and nab-paclitaxel

4 weeks

3 visits per cycle (in-person)

Randomized Phase 2

Evaluate the efficacy of paricalcitol when added to gemcitabine and nab-paclitaxel

Until disease progression or adverse events

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Nab-paclitaxel
• Paricalcitol

Trial Overview The study tests adding paricalcitol (IV or Oral) to standard chemo drugs gemcitabine and nab-paclitaxel in two stages: first checking safety (run-in phase) then assessing effectiveness (randomized phase). The goal is to see if paricalcitol improves treatment outcomes.

How Is the Trial Designed?

Group I: Gemcitabine + Nab-paclitaxel + Placebo Experimental Treatment 3 Interventions

* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis

Group II: Gemcitabine + Nab-paclitaxel + Paricalcitol oral Experimental Treatment 3 Interventions

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis

Group III: Gemcitabine + Nab-paclitaxel + Paricalcitol IV Experimental Treatment 3 Interventions

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

American Association for Cancer Research

Collaborator

Trials

9

Recruited

830+

Published Research Related to This Trial

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[2022]

Nab-paclitaxel has recently been introduced as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing promising improvements in patient outcomes after years of stagnation in treatment options.

The review highlights the unique mechanism of action of nab-paclitaxel, particularly its interaction with albumin and SPARC, which may enhance its efficacy in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. Al-Batran, SE., Geissler, M., Seufferlein, T., et al.[2015]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

In a retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., et al.[2022]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03520790

NCT03520790 | Paricalcitol Plus Gemcitabine and Nab ... This research study is a two stage study which consists of a safety run-in phase and a randomized phase 2 study which include subjects with ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03415854/

Clinical Trial: NCT03415854 The purpose of this study is to determine if the combination of paclitaxel protein bound, gemcitabine, cisplatin, paricalcitol are effective in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8003696/

Drug Repurposing Opportunities in Pancreatic Ductal ... First, in 2013, the combination of gemcitabine and nab-paclitaxel was approved for the first-line treatment of patients with metastatic PDAC, following the ...

4. trial.medpath.com trial.medpath.com/clinical-trial/fc196808364f6cc8/euctr2020-000073-24-ie-clinical-study-paricalcitol-gemcitabine-pancreatic-cancer

A Phase II clinical research study evaluating the effectiveness ... A Phase II clinical research study evaluating the effectiveness of paricalcitol in combination with gemcitabine/nab-paclitaxel in patients with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192994/

Phase II clinical trial of nab‐paclitaxel plus cisplatin plus ... We achieved an ORR of 71% with two CRs, 12‐month OS of 65%, and median survival of 16+ months. The current phase II study was performed to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04617067

Study Details | NCT04617067 | Paricalcitol Trial: Phase II, ... The trial is designed to establish whether adding a vitamin D analogue, Paricalcitol, to standard chemotherapy treatment, Gemcitabine and Nab-paclitaxel, can ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009835/

A phase 1 open label, dose escalation study of intravenous ... In summary, paricalcitol can be safely combined with gemcitabine in patients with advanced cancer in doses up to 7 mcg/kg weekly IV.

8. dana-farber.org dana-farber.org/clinical-trials/18-021

Vitamin D Receptor Agonist Paricalcitol plus Gemcitabine ... SAFETY RUN-IN PHASE: Patients are randomized to 1 of 3 arms. ARM A: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine ...